Re: Magnesium orotate, uridine, arachidonic acid » Larry Hoover

> CDP-choline shows evidence of substantially boosting blood uridine levels. I don't think there's enough in baby formula to make a big difference, unless you tried to subsist on it.> > Here's something I came across while investigating the biochemistry of uridine. > > Orotic acid. > > We've heard of that, lots of times. Lithium orotate is the salt of lithium cations and oratic acid anions.> > Another name for orotic acid is uracil-6-carboxylic acid.> > Uracil is one ribose sugar away from uridine.> > So, maybe all those people thinking they were treating themselves with lithium were feeling better from the orotic acid?> > I'm speculating, on that.> > However, magnesium orotate is quite inexpensive, here:> http://vitanetonline.com/description/71060-K/vitamins/Magnesium-Orotate/> > Other sources are four times that cost, and I don't know why.> > Lar

I wonder if the cost is related to the amount of elemental magnesium. The KAL brand doesn't say, but some others I've seen do and it's low. Examples:

Beyond a Century sells magnesium orotate in powder form. 1/4 tsp equals 73 mg elemental magnesium, and there are 200 of those in their container; you'd need 1 and 3/4 tsp daily to get 511 mg of magnesium. At their price of $22.50, that's 90 cents per day.

If the KAL brand you linked to has the same amount of elemental magnesium per unit, then 200 mg is 14 mg of magnesium. To get approx 500 mg/day you'd need 35 capsules a day, at $6.83 for 60 count, that's approx 11 cents per unit, or $3.85/day.

I'm going to order from BAC. I'm sure it will taste terrible though.

Speaking of orotic acid....

At the bottom of this page about lithium orotate there's some discussion of orotic acid and specifically magnesium orotate, including that "the body preferentially uses magnesium orotate for promoting uridine synthesis".

"The enzyme orotate phosphoribosyltransferase (OPRTase), which is found in organisms ranging from yeast to humans, is responsible for catalyzing the first step in the conversion of orotic acid into uridine. It does so by facilitating the attachment of a ribose plus phosphate group to OA. The net result is the formation of a molecule named OMP (orotidine 5'-monophosphate), which in turn is the immediate precursor to UMP (uridine 5'-monophosphate).

Because the enzyme OPRTase requires magnesium ions for its activity, some researchers wondered whether a magnesium complex of orotic acid might be involved in binding orotate to the enzyme.10 They found that the true substrate for OPRTase is not orotate itself but rather a magnesium orotate complex. The fact that the complex is electrically neutral compared to the negatively charged orotate ion means that the complex is more easily transportable to the active site of the enzyme.10 These researchers suggested that the magnesium complex helps position orotate within the enzyme in the proper orientation for conversion to OMP. In the process the magnesium ion in the complex gets exchanged with the magnesium ion bound to the active site of the enzyme, the net result being that one magnesium ion is released.

So far, so good. Following up on Nieper's hint, we see that orotate-and specifically magnesium orotate-can interact with the pentose phosphate pathway (PPP) to generate OMP and ultimately uridine."

"It now appears that the syntheses of phosphatidylcholine [PC] and the other major membrane phospholipids also depend on precursor availability. The main circulating precursor is cytidine (or, in humans, uridine), a compound that is not present in the final phospholipid product, but which, when phosphorylated to CTP, controls a key step in phosphatide synthesis (i.e., the combining of phosphocholine and CTP to form endogenous cytidyldiphosphocholine [CDP-choline])."

So uridine increases phosphatidylcholine?

In his next paragraph he mentions arachidonic acid,

"These observations have led to a new strategy for developing drugs to treat strokes and brain injury, i.e., diminish the ultimate size of the damaged area (which usually expands during the initial week after the stroke, because of the release of toxic compounds, like arachidonic acid oxidation products from nearly dying cells), and facilitate the regrowth of damaged axons and synapses by surviving neurons, by promoting the synthesis of PC (which sopps up free arachidonic acid). Both effects can be obtained experimentally, by giving a drug, Citicoline, that breaks down to blood choline and cytidine (uridine in humans), or by giving a constituent of infant formulas, UMP, that raises blood uridine levels. The blood changes increase CTP and phosphocholine levels in the brain, promoting the incorporation of excess free arachidonic acid into PC and thus increasing neuronal membranes."

"They examined the brains of the depressed rats and compared them with brains from normal rats. Surprisingly, they found that the main difference between the two types of rats was in omega-6 fatty acid levels and not omega-3 fatty acid levels. Specifically, they discovered that brains from rats with depression had higher concentrations of arachidonic acid, a long-chain unsaturated metabolite of omega-6 fatty acid. ...

"The finding that in the depressive rats the omega-3 fatty acid levels were not decreased, but arachidonic acid was substantially increased as compared to controls is somewhat unexpected," admits Dr. Green. "But the finding lends itself nicely to the theory that increased omega-3 fatty acid intake may shift the balance between the two fatty acid families in the brain, since it has been demonstrated in animal studies that increased omega-3 fatty acid intake may result in decreased brain arachidonic acid."

If it's arachidonic acid reduction that is significant aside from or in addition to increasing omega-3, then it suggests that if you eat a high animal-fat diet you'd benefit from increasing uridine via magnesium orotate and/or CDP-choline, correct? Is it possible too that if you don't have enough uridine that proper synethesis of phosphatidylcholine is not what it should be? Iow, increasing uridine and thus PC is different from simply ingesting lecithin?

I'm looking up arachidonic acid and see that it promotes inflammation which is also associated with depression.